chrysin and Disease-Models--Animal

Non-alcoholic steatohepatitis (NASH) is a chronic liver disease histologically characterized by liver steatosis, hepatocellular injury, inflammation and fibrosis, resulting in cirrhosis and hepatocellular carcinoma, but effective measures and obvious pathogenesis for NASH remain elusive. Chrysin (CH) has been reported to have anti-inflammatory effects but shows lower bioavailability.. In this study, a chrysin nanoliposome (CH-NL) was first prepared and characterized. Then, we used the methionine-choline-deficient (MCD) diet to induce a mouse model of NASH. Finally, the effects of CH and CH-NL on NASH were evaluated in the liver of NASH mice.. The results showed that CH or CH-NL significantly reduced the accumulation of lipids in hepatocytes, alleviated liver injury, decreased the generation of radical oxygen species, and attenuated the accumulation of collagen fibre in the liver of NASH mice. In addition, CH and its nano-liposomes markedly inhibited the production of inflammatory cytokines and inflammatory cell infiltration in the liver of NASH mice. Further studies found that CH-NL and CH-NL downregulated the MCD diet-induced activation of Toll-like receptor 4 (TLR4) signalling pathway in the liver of mice.. CH and its nanoliposome alleviated MCD diet-induced NASH in mice, which might be through inhibiting TLR4 signalling pathway.

Topics: Animals; Choline; Diet; Disease Models, Animal; Flavonoids; Liver; Methionine; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Toll-Like Receptor 4

Amiodarone is the first choice for the treatment of arrhythmia, but it is easy to cause extravasation during infusion, after extravasation, it often cause skin injury. The healing of skin injury induced by amiodarone is an inflammatory process. Chrysin, a natural flavonoid, has been investigated to have anti-inflammatory and antioxidant effects. It was reported that chrysin can promote wound healing. So this study aims to investigate the effect of chrysin on amiodarone extravasation-induced skin injury model in rats.. The rat model of skin extravasation injury was established by subcutaneous injection of 0.5 mL of amiodarone. After successful modeling, the rats were randomly assigned to the five groups: control group, 10% DMSO group, and low-dose, medium-dose, and high-dose chrysin groups (10, 20 and 40 mg/mL). The extravasation injury model was given locally on the same day for seven days. On day 0, 3, 7 and 10 of administration, the lesion's image were taken to calculate the area, and the tissue of the lesion were collected for H&E staining. Then, the level of IL-6 and TNF-α were measured by ELISA, and the protein expression level of bFGF in the wound tissue were detected by immunohistochemical staining.. It was found that chrysin groups (20 and 40 mg/mL) compared to contronl group and 10% DMSO solvent group significantly decreased area injury, IL-6 and TNF-α(P < 0.05) on day 3, 7, 10. On the other hand, the chrysin group (40 mg/mL) compared to contronl group and 10% DMSO group significantly increase bFGF(P < 0.05) on day 3, 7.. Chrysin were effective in reducing injury area, reducing inflammation, and promoting the secretion of bFGF, it can promote the healing of skin injury induced by amiodarone extravasation in rats. These findings provide a good theoretical and experimental basis for the prevention and treatment of amiodarone extravasation-induced skin injury, and provide evidence for finding potential healing agents for the prevention and treatment of amiodarone and other corrosive extravasation-induced injuries from the molecular and cytological levels, thus solving the clinical problems.

Topics: Amiodarone; Animals; Anti-Inflammatory Agents; Cell Proliferation; Disease Models, Animal; Endothelial Cells; Fibroblast Growth Factor 2; Fibroblasts; Flavonoids; Interleukin-6; Rats, Sprague-Dawley; Skin; Skin Diseases; Tumor Necrosis Factor-alpha; Wound Healing

The chrysin has properties of low aqueous solubility, bioavailability and absorption, and its effect on hepatic ischaemia-reperfusion (HIR) remains unclear. Thus, we prepared a liposomal chrysin (LC) and explored its effect and potential mechanism on HIR.. A thin-film dispersion method was used to prepare LC, and a mouse HIR model was used. Mice were pre-treated with LC (100 mg/kg) or placebo by gavage feeding at 16.5 h, 8.5 h, 0.5 h before modelling.. The average particle sizes, polydispersity index, zeta potential, encapsulation efficiency and drug loading of LC were 129 ± 13.53 nm, 0.265 ± 0.021, -34.46 ± 4.14 mV, 95.03 ± 2.17%, 16.4 ± 0.8%. The concentration of chrysin in plasma and liver tissue by LC administration increased 2.54 times and 1.45 times. LC pre-treatment reduced HIR-induced liver injury and inhibited cell apoptosis. Besides, LC pre-treatment decreased reactive oxygen species and malondialdehyde and inhibited the inflammation response indicated by lower IL-6, TNF-α, infiltration of neutrophils. Further, LC pre-treatment significantly decreased NLRP3 activation, evidenced by reduced cleaved caspase-3, NLRP3, ASC, cleaved caspase-1 and IL-1β expression.. LC has good biocompatibility, and it could attenuate HIR-induced injury. Its mechanism was associated with NLRP3 inflammasome inhibition, and LC might be an effective drug for treating and preventing HIR-induced injury.

Topics: Animals; Apoptosis; Disease Models, Animal; Flavonoids; Inflammasomes; Liposomes; Liver Diseases; Male; Mice; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein; Particle Size; Reactive Oxygen Species; Reperfusion Injury

Parkinson's disease (PD) is the second most progressive neurodegenerative disorder of the central nervous system in the elderly, causing motor impediments and cognitive dysfunctions. Dopaminergic (DA) neuron degeneration and α-synuclein (α-Syn) accumulation in substantia nigra pars compacta are the major contributors to this disease. At present, PD remains untreatable with a huge burden on the quality of life. Therefore, we attempt to explore novel treatment strategies by detecting effective drugs that stop or arrest PD's progression

Topics: alpha-Synuclein; Animals; Caenorhabditis elegans; Disease Models, Animal; Dopaminergic Neurons; Flavonoids; Parkinson Disease; Quality of Life

In pulmonary arterial hypertension (PAH), right ventricular failure is accompanied by metabolic alterations in cardiomyocytes, which may be due to mitochondrial dysfunction and decreased energy production. Chrysin (CH) is a phytochemical with pharmacological activity that is involved in the regulation of mitochondrial biogenesis. The present study investigated the role of CH in the right ventricle (RV) by analyzing the cardiac transcriptome and metabolome of a SU5416(a vascular endothelial growth factor receptor blocker, /hypoxia (Su/Hx) rat model of PAH. RNA‑sequencing of the RV transcriptome between Su/Hx, Su/Hx with CH (Su/Hx + CH) and control groups, extracellular matrix (ECM) organization and ECM‑receptor interaction‑associated genes were upregulated in the RV of Su/Hx but not Su/Hx + CH rats. Furthermore, expression of mitochondrial function‑, energy production‑, oxidative phosphorylation‑ and tricarboxylic acid (TCA) cycle‑associated genes was decreased in the RV of Su/Hx rats; this was reverse by CH. Metabolomic profiling analysis of Su/Hx and Su/Hx + CH rats showed no significant changes in glycolysis, TCA cycle, glutathione, NADH or NADPH. By contrast, in the RV of Su/Hx rats, decreased adenylate energy charge was partially reversed by CH administration, suggesting that CH was involved in the improvement of mitochondrial biogenesis. Reverse transcription‑quantitative PCR analysis revealed that expression of peroxisome proliferator‑activated receptor γ, a master regulator of fatty acid metabolism and mitochondrial biogenesis, was increased in the RV of Su/Hx + CH rats. CH ameliorated cardiac abnormality, including cardiac fibrosis, RV hypertrophy and PH. The present study suggested that CH altered patterns of gene expression and levels of mitochondrial metabolites in cardiomyocytes, thus improving RV dysfunction in a Su/Hx PAH rat model.

Topics: Animals; Disease Models, Animal; Flavonoids; Heart Ventricles; Hypertension, Pulmonary; Organelle Biogenesis; Pulmonary Arterial Hypertension; Rats; Rats, Sprague-Dawley; Vascular Endothelial Growth Factor A

Chrysin (CHR) is a flavonoid with extensive pharmacological activity. The molecular formula of CHR is C

Topics: Adjuvants, Immunologic; Animals; Cancer Vaccines; CD8-Positive T-Lymphocytes; Disease Models, Animal; Flavonoids; Immunity; Interleukin-12; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Signal Transduction; STAT4 Transcription Factor

Colorectal cancer is one of the primary causes of cancer-related mortality worldwide. The tumor microenvironment contains growth factors; inflammatory chemokines, matrix metalloproteinases, and pro-oxidants leading to cancer development and progression. Phytochemicals have been used as the main source of anti-cancer agents. Accordingly, the effect of two natural flavonoids (Chrysin and Daidzein) was investigated on the level of amphiregulin (AREG), chemokine ligand (CXCL1), and matrix metalloproteinase-9 (MMP-9) in 1, 2-dimethylhydrazine dihydrochloride (DMH) induced colorectal cancer. Rats were injected by DMH (40 mg/kg/week S.C.) for 16 weeks concomitantly with 2% dextran sodium sulfate (DSS) in drinking water for three cycles. Rats were orally treated with chrysin (125 and 250 mg/kg) and daidzein (5 and10 mg/kg) three times/week for the last 8 weeks. DMH + DSS group showed a significant (P < 0.05) increase in the levels of AREG (2386 ± 18 vs 1377 ± 10 pg/ml), CXCL1 (18 ± 0.9 vs 6 ± 0.83 g/ml), MMP-9 (1355 ± 88 vs 452 ± 7 pg/ml) compared to normal rats. These findings were associated with a potent antioxidant activity against cytochrome P450 2E1; (CYP2E1). Histopathological findings of the DMH + DSS group showed focal hyperplasia of the mucosa lining overlying crypts with moderate inflammation, dysplastic epithelial cells, and loss of goblet cells. Chrysin and daidzein treatment significantly (P < 0.05) restored the biochemical alterations and reverted histopathological findings near to the normal status. Moreover, chrysin and daidzein exerted anticancer activity against SW620 cells that were associated with decreased the protein expression of p-ERK/ERK and p-AKT/AKT. In conclusion, this study highlighted the potential anticancer role of chrysin and daidzein in the treatment of colon cancer.

Topics: 1,2-Dimethylhydrazine; Amphiregulin; Animals; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Transformation, Neoplastic; Chemokine CXCL1; Colon; Colorectal Neoplasms; Cytochrome P-450 CYP2E1; Dextran Sulfate; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Flavonoids; Humans; Isoflavones; Male; Matrix Metalloproteinase 9; Oxidative Stress; Proto-Oncogene Proteins c-akt; Rats; Signal Transduction

This experimental study evaluated the anti-asthmatic capacity of the dihydroxyflavone chrysin in the settings of ovalbumin (OVA)-induced allergic inflammation.. The parameters that were used to assess the anti-asthmatic activity of chrysin included the specific airway resistance to histamine, the sensitivity to a chemically induced cough and the activity of chrysin on the ciliary beat frequency (CBF) of the respiratory epithelium. The anti-inflammatory potential was confirmed by the measurement of cytokine concentrations Th2 (IL-4, IL-5 and IL-13), Th1 (Granulocyte-macrophage colony-stimulating factor [GM-CSF], INF-γ and IL-12), leucocyte count in the bronchoalveolar lavage fluid (BALF) and growth factor TBF-β1 in lung homogenate.. Chronic administration of chrysin (30 mg/kg/day for 21 days) to OVA-sensitised guinea pigs showed bronchodilatory activity comparable to that of long-acting β 2 receptors agonist (LABA) salmeterol. Chrysin revealed antitussive efficiency but was not able to abolish the negative effect of OVA on CBF. Chrysin managed to ameliorate the progression of chronic airway inflammation by decreasing the count of eosinophils, lymphocytes and basophils, IL-5, L-13, GM-CSF, INF-γ in BALF, and TGF-β1 in lung homogenate.. The acquired results support the complex anti-asthmatic profile of chrysin. The flavone may represent an attractive compound for further studies concerning the prevention or treatment of asthma.

Topics: Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Antitussive Agents; Asthma; Bronchoalveolar Lavage Fluid; Cough; Cytokines; Disease Models, Animal; Disease Progression; Flavonoids; Guinea Pigs; Inflammation; Male; Ovalbumin; Salmeterol Xinafoate

The incidence of myocardial dysfunction caused by sepsis is high, and the mortality of patients with sepsis can be significantly increased. During sepsis, oxidative stress and inflammation can lead to severe organ dysfunction. Flavone chrysin is one of the indispensable biological active ingredients for different fruits and vegetables and has antioxidant and anti-inflammatory properties. However, it is not clear whether chrysin is an effective treatment for heart dysfunction caused by sepsis. We found that it had protective effects against the harmful effects caused by LPS, manifested in improved survival, normalized cardiac function, improved partial pathological scores of myocardial tissue, and remission of apoptosis, as well as reduced oxidative stress and inflammation. Mechanism studies have found that chrysin is an important antioxidant protein, a key regulator of heme oxygenase 1 (HO-1). We found that HO-1 levels were increased after LPS intervention, and chrysin further increased HO-1 levels, along with the addition of Nrf2, a regulator of antioxidant proteins. Pretreatment with PD98059, an extracellular signal-regulated kinase-specific inhibitor, blocked chrysin-mediated phosphorylation of Nrf2 and the nuclear translocation of Nrf2. The protective effect of chrysin on sepsis-induced cardiac dysfunction was blocked by ZnPP, which is a HO-1 blocker. Chrysin increased antioxidant activity and reduced markers of oxidative stress (SOD and MDA) and inflammation (MPO and IL-1β), all of which were blocked by ZnPP. This indicates that HO-1 is the upstream molecule regulating the protective effect of chrysin. Thus, by upregulation of HO-1, chrysin protects against LPS-induced cardiac dysfunction and inflammation by inhibiting oxidative stress.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cell Line; Disease Models, Animal; Flavonoids; Heart Diseases; Heme Oxygenase-1; Inflammation Mediators; Lipopolysaccharides; Male; Membrane Proteins; Mice, Inbred C57BL; Myocytes, Cardiac; NF-E2-Related Factor 2; Oxidative Stress; Rats; Sepsis; Signal Transduction; Ventricular Function, Left

Oxidative stress and inflammation play a critical role in the etiopathogenesis of bronchopulmonary dysplasia (BPD). The aim of this study was to evaluate the preventive effect of Chrysin (CH), an antioxidant, antiinflammatory, antiapoptotic and antifibrotic drug, on hyperoxia-induced lung injury in a neonatal rat model.. Forty infant rats were divided into four groups labeled the Control, CH, BPD, and BPD + CH. The control and CH groups were kept in a normal room environment, while the BPD and BPD + CH groups were kept in a hyperoxic (90-95%) environment. At the end of the study, lung tissue was evaluated with respect to apoptosis, histopathological damage and alveolar macrophage score as well as oxidant capacity, antioxidant capacity, and inflammation.. Compared to the BPD + CH and control groups, the lung tissues of the BPD group displayed substantially higher levels of MDA, TOS, TNF-α, and IL-1β (p < 0.05). While the BPD + CH group showed similar levels of TNF-α and IL-1β as the control group, MDA and TOS levels were higher than the control group, and significantly lower than the BPD group (p < 0.05). The BPD group exhibited considerably lower levels of TAS, SOD, GSH, and GSH-Px in comparison to the control group (p < 0.05). The BPD and BPD + CH groups exhibited higher mean scores of histopathological damage and alveolar macrophage when compared to the control and CH groups (p ≤ 0.0001). Both scores were found to be lower in the BPD + CH group in comparison to the BPD group (p ≤ 0.0001). The BPD + CH group demonstrated a significantly lower average of TUNEL and caspase-3 positive cells than the BPD group.. We found that prophylaxis with CH results in lower histopathological damage score and reduces apoptotic cell count, inflammation and oxidative stress while increasing anti-oxidant capacity.

Topics: Animals; Animals, Newborn; Antioxidants; Apoptosis; Bronchopulmonary Dysplasia; Caspase 3; Disease Models, Animal; Flavonoids; Glutathione Peroxidase; Glutathione Reductase; Hyperoxia; Interleukin-1beta; Lung Injury; Macrophages, Alveolar; Malondialdehyde; Oxidants; Oxidative Stress; Oxygen; Rats, Wistar; Superoxide Dismutase; Tumor Necrosis Factor-alpha

When Zika virus emerged as a public health emergency there were no drugs or vaccines approved for its prevention or treatment. We used a high-throughput screen for Zika virus protease inhibitors to identify several inhibitors of Zika virus infection. We expressed the NS2B-NS3 Zika virus protease and conducted a biochemical screen for small-molecule inhibitors. A quantitative structure-activity relationship model was employed to virtually screen ∼138,000 compounds, which increased the identification of active compounds, while decreasing screening time and resources. Candidate inhibitors were validated in several viral infection assays. Small molecules with favorable clinical profiles, especially the five-lipoxygenase-activating protein inhibitor, MK-591, inhibited the Zika virus protease and infection in neural stem cells. Members of the tetracycline family of antibiotics were more potent inhibitors of Zika virus infection than the protease, suggesting they may have multiple mechanisms of action. The most potent tetracycline, methacycline, reduced the amount of Zika virus present in the brain and the severity of Zika virus-induced motor deficits in an immunocompetent mouse model. As Food and Drug Administration-approved drugs, the tetracyclines could be quickly translated to the clinic. The compounds identified through our screening paradigm have the potential to be used as prophylactics for patients traveling to endemic regions or for the treatment of the neurological complications of Zika virus infection.

Topics: Animals; Antiviral Agents; Artificial Intelligence; Chlorocebus aethiops; Disease Models, Animal; Drug Evaluation, Preclinical; High-Throughput Screening Assays; Immunocompetence; Inhibitory Concentration 50; Methacycline; Mice, Inbred C57BL; Protease Inhibitors; Quantitative Structure-Activity Relationship; Small Molecule Libraries; Vero Cells; Zika Virus; Zika Virus Infection

Psoriasis is a common non-contagious chronic inflammatory skin lesion, with frequent recurrence. It mainly occurs due to aberrant regulation of the immune system leading to abnormal proliferation of skin cells. However, the pathogenic mechanisms of psoriasis are not fully understood. Although most of the current therapies are mostly efficient, the side effects can result in therapy stop, which makes the effectiveness of treatment strategies limited. Therefore, it is urgent and necessary to develop novel therapeutics. Here, we investigated the efficacy of chrysin, a plant flavonoid, which we previously reported to possess strong antioxidant and anti-inflammatory effects, against psoriasis-like inflammation. Our results revealed that chrysin significantly attenuated imiquimod-induced psoriasis-like skin lesions in mice, and improved imiquimod-induced disruption of skin barrier. Moreover, the TNF-α, IL-17A, and IL-22-induced phosphorylation of MAPK and JAK-STAT pathways, and activation of the NF-κB pathway were also attenuated by chrysin pretreatment of epidermal keratinocytes. Most importantly, chrysin reduced TNF-α-, IL-17A-, and IL-22-induced CCL20 and antimicrobial peptide release from epidermal keratinocytes. Thus, our findings indicate that chrysin may have therapeutic potential against inflammatory skin diseases. Our study provides a basis for further investigating chrysin as a novel pharmacologic agent and contributes to the academic advancement in the field of Chinese herbal medicine.

Topics: Animals; Antimicrobial Cationic Peptides; Chemokine CCL20; Disease Models, Animal; Down-Regulation; Epidermis; Flavonoids; Humans; Hyperplasia; Imiquimod; Inflammation; Interleukin-17; Interleukin-22; Interleukins; Keratinocytes; Male; MAP Kinase Signaling System; Mice, Inbred BALB C; NF-kappa B; Phosphorylation; Psoriasis; RNA, Messenger; Skin; Tumor Necrosis Factor-alpha

This experimental study was conducted to evaluate the possible effects of orally administered chrysin on acute pancreatitis.. Twenty four rats were procured. The animals were randomly divided into four groups. In Group I, only vehicle solution (5% dimethylsulfoksid) was administered, and in Group II, chrysin dissolved in the vehicle solution was administered for six days. In Group III and Group IV cerulein was administered to induce acute pancreatitis. In Group III, only vehicle solution was administered, and in Group IV, chrysin dissolved in the vehicle solution was administered orally for six days. Blood samples were analyzed and the pancreatic tissue specimens were evaluated for histopathological examination.. Group III and Group IV, exhibited markedly higher levels of serum WBC, amylase, and lipase, compared with Groups I and II. In the pancreatitis induced groups, CRP and TOS values were found to be significantly higher. In Group II and Group IV, TAS values were significantly higher. The highest calculated OSI values were observed in Group III. Group IV OSI values were significantly lower than those in Group III and even in Group I. Noticeable histopathological changes were identified in the pancreatitis induced Groups III and IV. Compared with Group III, the extent and severity of pancreatic injuries were markedly lower in Group IV.. Chrysin application reduced oxidative stress and histopathological parameters. The present study shows that chrysin can be used to treat pancreatic diseases.. Acute pancreatitis, Cerulein, Chrysin.. Si tratta di uno studio sperimentale finalizzato alla valutazione dei possibili effetti della somministrazione orale di Chrysina sulla pancreatite acuta. Sono stati utilizzati 24 ratti divisi a random in quattro gruppi. Nel primo gruppo è stata somministrata agli animali soltanto la soluzione eccipiente (5% dimethylsulfoksid - DMSO). Nel Gruppo II è stata somministrata per 6 giorni la Chrysina disciolta nella stessa soluzione veicolo. Nel Gruppo III e nel Gruppo IV è stata somministrata Ceruleina per indurre una pancreatite acuta, Nel III Gruppo è stata somministrata la sola soluzione veicolo, mentre nel IV Gruppo è stata somministrata per 6 giorni la Chrysina disciolta nella soluzione veicolante. Sono stati analizzati campioni di sangue e sono stati prelevati campioni di tessuto pancreatico per esame istopatologico. Nei Gruppi III e IV si sono riscontrati più elevati livelli di leucocitosi, di amilasi e lipasi in paragone con i Gruppi I e II. Nei gruppi in cui è stata indotta la pancreatite acuta sono stati riscontrati valori significativamente più alti di Proteina C Reattiva (CRP) e un più elevato stato totale di ossidanti (TOS). Nei Gruppi II e IV i valori di stato totale di antiossidanti (TAS) sono stati rilevati significativamente più elevati. I più alti valori calcolati di Stress ossidative Index (OSI) sono stati riscontrati nel Gruppo III. Nel IV Gi valori di OSI sono risultati significativamente inferiori rispetto a quelli dei Gruppi III ed anche I. Notevoli alterazioni istopatologiche sono state osservate nei gruppi III e IV di pancreatite acuta indotta. A confronto con il Gruppo III la diffusione e la gravità dei danni pancreatici sono stati rilevati significativamente minori nel Gruppo IV. L’utilizzo della Chrysina riduca dunque lo stress ossidativo e i parametri istopatologici, e dunque questo studio indica che la Chrysina può essere usata per il trattamento delle patologie del pancreas.

Topics: Acute Disease; Animals; Disease Models, Animal; Flavonoids; Pancreas; Pancreatitis; Random Allocation; Rats; Rats, Wistar

Chrysin (CH) is the main ingredient of many medicinal plants. Our previous study showed that CH could suppress hypoxia-induced pulmonary arterial smooth muscle cells proliferation and alleviate chronic hypoxia-induced pulmonary hypertension by targeting store-operated Ca entry (SOCE)-[Ca]i pathway. In this study, we investigated the effect of CH on monocrotaline-induced pulmonary hypertension (MCTPH) and the mechanism behind it. Results show that, in MCTPH model rats, (1) CH significantly reduced the enhancement of right ventricular pressure, right ventricular hypertrophy, and pulmonary vascular remodeling; (2) CH markedly suppressed the promotion of SOCE and [Ca]i in pulmonary arterial smooth muscle cells; and (3) CH obviously inhibited the MCT-upregulated proliferating cell nuclear antigen, TRPC1, TRPC4, and TRPC6 expression in distal pulmonary arteries. These results demonstrate that CH likely alleviates MCTPH by targeting TRPC1,4,6-SOCE-[Ca]i pathway.

Topics: Animals; Antihypertensive Agents; Arterial Pressure; Calcium Signaling; Disease Models, Animal; Flavonoids; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Monocrotaline; Muscle, Smooth, Vascular; Pulmonary Artery; Rats, Sprague-Dawley; TRPC Cation Channels; Vascular Remodeling; Ventricular Function, Right; Ventricular Pressure; Ventricular Remodeling

We investigated the effects of chrysin (CHR) on nonalcoholic fatty liver disease (NAFLD) in mice. The NAFLD mouse model was established using a diet deficient in methionine and choline (MCD). CHR was shown to attenuate MCD-induced hepatic fat accumulation, increase very low-density lipoprotein (VLDL) secretion, and decrease hepatic oxidative stress in NAFLD mice. Inhibition of oxidative stress or direct suppression of protein kinase C (PKC) by CHR significantly reduced PKC activity in the liver, leading to a decrease in inhibitory phosphorylation of hepatocyte nuclear factor 4α (HNF4α). The resulting activation of HNF4α led to induced transcription of apolipoprotein B and VLDL secretion. Together, these results show that CHR effectively ameliorates MCD-induced fatty liver in NAFLD mice by targeting the hepatic oxidative stress/PKC/HNF4α signaling pathway.

Topics: Animals; Choline Deficiency; Diet; Disease Models, Animal; Flavonoids; Hep G2 Cells; Hepatocyte Nuclear Factor 4; Hepatocytes; Humans; Lipoproteins, VLDL; Male; Methionine; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Protein Kinase C; Secretory Pathway; Signal Transduction; Treatment Outcome

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among the elderly population. Vascular endothelial growth factor (VEGF) is essential for choroidal neovascularization (CNV) development in advanced, wet AMD. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid with anti-inflammatory, anti-oxidative, and anti-angiogenic effects. We hypothesized that intravitreally injected chrysin may inhibit CNV due to its inhibitory effect on angiogenesis. To determine the effects of chrysin on an experimental CNV model, we induced CNV in Brown Norway rats with a diode laser. One week later, rats were injected intravitreally with chrysin in the right eye and vehicle in the left eye. The following week, we evaluated chrysin's effects via the CNV grade assessed with fluorescein angiography and histologic analyses. Hypoxia-inducible factor-1 alpha (HIF-1α) and VEGF expression in the retina/choroid complex were also measured in both eyes. The mean CNV grade was significantly lower in chrysin-treated vs. control eyes (2.34 ± 1.14 vs. 2.97 ± 1.05,

Topics: Angiogenesis Inhibitors; Animals; Choroidal Neovascularization; Disease Models, Animal; Flavonoids; Fluorescein Angiography; Fluorescent Antibody Technique; Hypoxia-Inducible Factor 1, alpha Subunit; Intravitreal Injections; Lasers; Macular Degeneration; Male; Rats; Rats, Inbred BN; Vascular Endothelial Growth Factor A

Persistent neuropathic pain poses a health problem, for which effective therapy or antidote is in dire need. This work aimed to investigate the pain-relieving effect of chrysin, a natural flavonoid with monoamine oxidase inhibitory activity, in an experimental model of neuropathic pain and elucidate mechanism(s).. Chronic constriction injury (CCI) was produced by loose ligation of sciatic nerve in mice. The pain-related behaviors were examined using von Frey test and Hargreaves test. The serotonin-related mechanisms were investigated by serotonin depletion with. Repeated treatment of CCI mice with chrysin (orally, two times per day for 2 weeks) ameliorated heat hyperalgesia and mechanical allodynia in a dose-dependent fashion (3-30 mg/kg). The chrysin-triggered pain relief seems serotonergically dependent, since its antihyperalgesic and antiallodynic actions were abolished by chemical depletion of serotonin by PCPA, whereas potentiated by 5-hydroxytryptophan (a precursor of 5-HT). Consistently, chrysin-treated neuropathic mice showed enhanced levels of spinal monoamines especially 5-HT, with depressed monoamine oxidase activity. Moreover, chrysin-evoked pain relief was preferentially counteracted by 5-HT. These findings confirm the antihyperalgesic and antiallodynic efficacies of chrysin, with spinal 5-HT

Topics: Animals; Disease Models, Animal; Flavonoids; Hot Temperature; Hyperalgesia; Mice; Mononeuropathies; Receptor, Serotonin, 5-HT1A

Pharmacological strategies aimed at co-activating peroxisome proliferator-activated receptor-gamma (PPAR-γ)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway have shown promising results in alleviating myocardial injury. The aim of the study was to evaluate the role of chrysin, a PPAR-γ agonist, in ischemia-reperfusion (IR)-induced myocardial infarction (MI) in rats and to explore the molecular mechanism driving this activity. To evaluate this hypothesis, chrysin (60 mg/kg, orally), PPAR-γ antagonist (GW9662, 1 mg/kg, intraperitoneally), or both were administered to rats for 28 days. On the 29th day, one-stage ligation of left anterior descending coronary artery for 45 min followed by 60 min of reperfusion was performed. Chrysin significantly decreased infarct size and improved cardiac functions following IR-induced MI. This improvement was corroborated by augmented PPAR-γ/Nrf2 expression as confirmed by immunohistochemistry and western blotting analysis. Chrysin exhibited strong anti-oxidant property as demonstrated by increased GSH and CAT levels and decreased 8-OHdG and TBARS levels. Our findings also imply that chrysin significantly inhibited inflammatory response as validated by decreased NF-κB, IKK-β, CRP, TNF-α and MPO levels. In addition, chrysin decreased TUNEL/DAPI positivity, a marker of apoptotic response and normalized cardiac injury markers. The histopathological and ultrastructural analysis further supported the functional and biochemical outcomes, showing preserved myocardial architecture. Intriguingly, co-administration with GW9662 significantly diminished the cardioprotective effect of chrysin as demonstrated by depressed myocardial function, decreased PPAR-γ/Nrf2 expression and increased oxidative stress. In conclusion, the present study demonstrates that co-activation of PPAR-γ/Nrf2 by chrysin may be crucial for its cardioprotective effect.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Cardiovascular Agents; Disease Models, Animal; Flavonoids; Hemodynamics; Inflammation Mediators; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Myocytes, Cardiac; NF-E2-Related Factor 2; Oxidative Stress; PPAR gamma; Rats, Wistar; Signal Transduction; Ventricular Function, Left

Pulmonary fibrosis is a chronic condition characterized by fibroblast proliferation, and the infiltration of inflammatory cells that can initiate local tissue hypoxia. In this study the effect of chrysin (50 mg/kg/orally) in a model of bleomycin (BLM)-induced pulmonary fibrosis was studied. Chrysin managed to decrease mortality rate associated with BLM instillation and it managed to improve lung architecture and lung fibrosis by decreasing hydroxyproline content and transforming growth factor-β1 (TGF-β1) protein expression. Chrysin showed anti-inflammatory effect displayed by the decrease in inflammatory cells infiltrates, the decline in permeability of the alveolar/capillary barrier and the reduction in lactate dehydrogenase (LDH) activity. Chrysin demonstrated potent antioxidant effect by decreasing lipid peroxidation, increasing antioxidant defense mechanisms by increasing superoxide dismutase (SOD) activity and reduced glutathione (GSH) content. Additionally, the effect of chrysin on nitric oxide (NOx) content was assessed, where chrysin decreased NOx, increased the protein expression of endothelial nitric oxide synthase (eNOS), and decreased inducible nitric oxide synthase (iNOS) protein expression. Chrysin also succeeded in decreasing thioredoxin-interacting protein (TXNIP), the negative regulator of thioredoxin system, showing potent antioxidant effect. Finally, both tissue and bronchoalveolar lavage fluid contents of hypoxia inducible factor one alpha (HIF1α) were decreased by chrysin indicating that chrysin decreased local tissue hypoxia. In conclusion, this study exposed a possible proof that chrysin could mitigate pulmonary fibrosis induced by BLM through its anti-inflammatory, antioxidant, antifibrotic effects and its effect in alleviating hypoxia.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Bleomycin; Cell Cycle Proteins; Cell Hypoxia; Disease Models, Animal; Flavonoids; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation Mediators; Lipid Peroxidation; Lung; Male; Nitric Oxide; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Oxidative Stress; Pneumonia; Pulmonary Fibrosis; Rats, Sprague-Dawley; Signal Transduction

Isoniazid (INH) is among the most important anti-tuberculosis agents widely prescribed. However, its clinical use is restricted due to its severe side effects associated with neurotoxicity. The aim of the present study was to investigate the neuroprotective effects of chrysin (CR), a natural antioxidant, against INH-induced neurotoxicity in rats. The rats were treated orally with INH (400 mg/kg body weight) alone or with CR (25 and 50 mg/kg body weight) for 7 consecutive days. INH administration significantly increased brain lipid peroxidation and resulted in a significant decrease in antioxidant biomarkers including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH). INH treatment also increased levels of nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), glial fibrillary acidic protein (GFAP) and activities of p38α mitogen-activated protein kinase (p38α MAPK) while decreasing levels of neural cell adhesion molecule (NCAM). Double immunofluorescence expressions of c-Jun N-terminal kinase (JNK) and Bcl-2 associated X protein (Bax) in brain tissues were increased after INH administration. Furthermore, INH increased mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO1), glutamate-cysteine ligase modifier subunit (Gclm), glutamate cysteine ligase catalytic subunit (Gclc), NF-κB, TNF-α, interleukin-1β (IL-1β), interleukin-6 (IL-6) and GFAP in rat brain tissues. Co-treatment with CR increased anti-oxidant capacity as well as regulated inflammation and apoptosis in brain. Additionally, molecular docking results showed that CR had the potential to interact with the active sites of TNF-α and NFκ-B. In conclusion, CR improved INH-induced brain oxidative damage, inflammation and apoptosis, possibly through their antioxidant properties.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Apoptosis Regulatory Proteins; Cerebral Cortex; Disease Models, Animal; Flavonoids; Inflammation Mediators; Isoniazid; Lipid Peroxidation; Male; Neurons; Neuroprotective Agents; Neurotoxicity Syndromes; Oxidative Stress; Rats, Sprague-Dawley

Metabolic syndrome (MS) is a major public health issue worldwide and fructose consumption has been associated with MS development. Recently, we showed that the dietary polyphenol chrysin is an effective inhibitor of fructose uptake by human intestinal epithelial cells. Therefore, our aim was to investigate if chrysin interferes with the development of MS induced by fructose in an animal model.. Adult male Sprague-Dawley rats (220-310 g) were randomly divided into four groups: (A) tap water (control), (B) tap water and a daily dose of chrysin (100 mg/kg) by oral administration (chrysin) (C) 10% fructose in tap water (fructose), and (D) 10% fructose in tap water and a daily dose of chrysin (100 mg/kg) by oral administration (fructose + chrysin). All groups were fed ad libitum with standard laboratory chow diet and dietary manipulation lasted 18 weeks.. Fructose-feeding for 18 weeks induced an increase in serum triacylglycerols, insulin and angiotensin II levels and in hepatic fibrosis and these changes did not occur in fructose + chrysin rats. Moreover, the increase in both systolic and diastolic blood pressure which was found in fructose-fed animals from week 14th onwards was not observed in fructose + chrysin animals. In contrast, the increase in energy consumption, liver/body, heart/body and right kidney/body weight ratios, serum proteins, serum leptin and liver triacylglycerols observed in fructose-fed rats was not affected by chrysin.. Chrysin was able to protect against some of the MS features induced by fructose-feeding.

Topics: Animals; Diet; Disease Models, Animal; Flavonoids; Fructose; Male; Metabolic Syndrome; Polyphenols; Rats; Rats, Sprague-Dawley

Inflammatory bowel disease (IBD) is a chronic disease that occurs in the intestinal tract. Phyto-ingredients have been evaluated for their ability to protect against IBD because of their anti-inflammatory activities. In our previous study, we identified a novel derivative of chrysin (HE-chrysin) using irradiation technology, which exhibited stronger anti-cancer activity in human colorectal cancer cells than the original chrysin. Here, to determine whether HE-chrysin is a new therapeutic candidate for IBD, we investigated the anti-inflammatory effects of HE-chrysin on bone marrow-derived dendritic cells (BMDCs) and dextran sodium salt (DSS)-induced colitis in mice. HE-chrysin more effectively inhibited BMDC maturation compared to chrysin, as demonstrated by the decreased levels of pro-inflammatory cytokines, surface molecules, antigen-presenting ability, and T cell proliferation/activation in lipopolysaccharide-stimulated BMDCs. These anti-inflammatory effects of HE-chrysin were regulated by mitogen-activated protein kinases and nuclear factor-κB. Furthermore, oral administration of HE-chrysin attenuated DSS-induced colitis symptoms and clinical signs in the mouse model. The protective effects of HE-chrysin treatment against colitis were mediated by decreasing Th1- and Th17-type cytokine levels. These results indicate that HE-chrysin is attractive candidate for IBD therapy.

Topics: Animals; Anti-Inflammatory Agents; Cell Proliferation; Colitis; Cytokines; Dendritic Cells; Dextran Sulfate; Disease Models, Animal; Female; Flavonoids; Inflammation Mediators; Inflammatory Bowel Diseases; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; NF-kappa B; Protective Agents; Signal Transduction

Topics: Animals; Bees; Diet, High-Fat; Disease Models, Animal; Flavanones; Flavonoids; Gastrointestinal Microbiome; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Non-alcoholic Fatty Liver Disease; Obesity; Pollen; Rutin; Schisandra

Gamma irradiation is a useful technology to change the physical and biological properties of natural molecules. In this study, we investigated whether gamma irradiation improve properties of chrysin as an anti-inflammatory candidates. Chrysin was converted into two compounds (CM1 and CM2) by gamma irradiation. We determined the therapeutic potential of these compounds in bone marrow-derived macrophages and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like skin lesions in Balb/c mice. The structural changes to chrysin led to the reduction of cytotoxicity without loss of anti-inflammatory properties in BMDMs. Purified CM2 inhibited lipopolysaccharide (LPS)-induced overexpression of nitric oxide, tumor necrosis factor-α, interleukin (IL)-6, and surface molecules without cytotoxicity in BMDMs, while CM1 revealed strong cytotoxicity. Furthermore, treatment with CM2 significantly alleviated AD-like skin symptoms and clinical signs in DNCB-induced AD mice model. The suppression of AD mediated by CM2 treatment was accompanied by decrease inflammatory T cell cytokines (IFN-γ, IL-5, IL-4, and IL-17). The chemical structure of CM2 and structural transformation mechanism were determined by nuclear magnetic resonance and mass spectrometry. Our study findings provide evidence that CM2 produced by gamma irradiation of chrysin can be an attractive therapeutic agent for AD.

Topics: Animals; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Disease Models, Animal; Female; Flavonoids; Gamma Rays; Irritants; Lymph Nodes; Mice, Inbred BALB C; Mice, Inbred C57BL; T-Lymphocytes

Ischemic stroke is one of the leading causes of death worldwide, and extensive efforts have focused on the neuroprotective strategies to minimize complications due to ischemia. This study aimed to examine neuroprotective potential of chrysin, as a natural potent antioxidative and anti-inflammatory agent in an animal model of bilateral common carotid artery occlusion and reperfusion (BCCAO/R).. Adult male Wistar rats (250-300 g) were randomly divided into 6 groups and submitted to either sham surgery or BCCAO/R after pretreatment with chrysin (10, 30 and 100 mg/kg, once daily, for 21 consecutive days) or saline containing %5 DMSO. To make the animal model of BCCAO/R, bilateral common carotid arteries were occluded for 20 min, followed by reperfusion. Subsequently, spatial cognitive performance was evaluated in a Morris water maze (MWM), hippocampal long-term potentiation (LTP) was recorded from hippocampal dentate gyrus region, after then the hippocampal tissue content of IL-1β and TNF-α were assayed using ELISA kits.. The results showed that pretreatment with chrysin significantly prevented BCCAO/R-induced cognitive and hippocampal LTP impairments (p < 0.001). Additionally, BCCAO/R- induced elevation in hippocampal content of IL-1β and TNF-α significantly (p < 0.01, p < 0.01 respectively) while pre-treatment with chrysin restored them (p < 0.01).. Our data confirm that chrysin could prevent brain inflammation and thereby prevents cognitive and LTP impairments due to cerebral ischemia. So it could be a promising neuroprotective agent against cerebrovascular insufficiency states.

Topics: Animals; Antioxidants; Brain Ischemia; Carotid Arteries; Carotid Artery, Common; Cognition; Cognitive Dysfunction; Disease Models, Animal; Encephalitis; Flavonoids; Hippocampus; Inflammation; Long-Term Potentiation; Male; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury

Oxidative stress and apoptosis have major roles in the progression of traumatic brain injury (TBI)-associated motor and cognitive deficits. The present study was aimed to elucidate the putative effects of chrysin, a natural flavonoid compound, against TBI-induced motor and cognitive dysfunctions and possible involved mechanisms.. Chrysin (25, 50 or 100 mg/kg) was orally administered to rats starting immediately following TBI induction by Marmarou's weight-drop technique and continuously for 3 or 14 days. Neurological functions, motor coordination, learning and memory performances, histological changes, cell apoptosis, expression of pro- and anti-apoptotic proteins, and oxidative status were assayed at scheduled time points after experimental TBI.. The results indicated that treatment with chrysin improved learning and memory disabilities in passive avoidance task, and ameliorated motor coordination impairment in rotarod test after TBI. These beneficial effects were accompanied by increased the concentrations of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH), decreased malondialdehyde (MDA) content, prevented neuronal loss, diminished apoptotic index, elevated the expression of anti-apoptotic Bcl-2 protein, and reduced the expression of pro-apoptotic Bax protein in the cerebral cortex and hippocampus tissues.. Our findings suggest that both anti-oxidative and anti-apoptotic properties of chrysin (especially in the dose of 100 mg/kg) are possible mechanisms that improve cognitive/motor deficits and prevent neuronal cell death after TBI.

Topics: Administration, Oral; Animals; Antioxidants; Apoptosis; Brain; Brain Injuries, Traumatic; Disease Models, Animal; Flavonoids; Learning; Male; Memory Disorders; Neuroprotective Agents; Oxidative Stress; Psychomotor Performance; Rats, Wistar

Due to the high rate of drug resistance among malignant melanoma cases, it seems necessary to introduce an efficient pharmaceutical approach to melanoma treatment. For this purpose, Curcumin (Cur) and Chrysin (Chr), two natural anti-cancers, were co-encapsulated in PLGA-PEG nanoparticles (NPs), characterized by DLS, FTIR and FE-SEM and investigated for their effects on MMPs, TIMPs and TERT genes expression in C57B16 mice bearing B16F10 melanoma tumours. The results showed that the expression of MMP-9, MMP-2 and TERT genes were significantly decreased in all treated groups compared to the control. This reduction had the highest amount in CurChr NPs group and then CurChr group for each three genes. Likewise, the expression of TIMP-1 and TIMP-2 genes was significantly increased in all treated groups, compared to the control. Combination groups showed the highest rise in expression of these two genes and the observed increase was greater in nano groups. Moreover, the highest melanoma tumour growth inhibition was detected for CurChr NPs, followed by CurChr = Cur NPs > Cur > Chr NP > Chr. Overall, it is speculated that the nano-combination of Cur and Chr into polymeric NPs with a one-step fabricated co-delivery system may be a promising and convenient approach to improve their efficiency in melanoma cancer therapy.

Topics: Animals; Capsules; Cell Proliferation; Curcumin; Disease Models, Animal; Disease Progression; Drug Carriers; Flavonoids; Gene Expression Regulation, Neoplastic; Male; Matrix Metalloproteinases; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Nanoparticles; Neoplasm Metastasis; Polyethylene Glycols; Polylactic Acid-Polyglycolic Acid Copolymer; Telomerase; Tissue Inhibitor of Metalloproteinases

Advanced glycation end products (AGEs) play a causative role in the development of diabetic nephropathy via induction of matrix protein deposition in kidneys. This study investigated inhibitory effects of chrysin, present in bee propolis and herbs, on glomerulosclerosis in db/db mice and AGEs-exposed renal mesangial cells. The in vivo study explored the demoting effects of 10 mg/kg chrysin on glomerular fibrosis in a type 2 diabetic model. Oral supplementation of chrysin inhibited the collagen fiber accumulation and α-smooth muscle actin (α-SMA) induction in periodic acid schiff-positive renal tissues of db/db mice. Moreover, treating db/db mice with chrysin diminished the level of AGEs increased in diabetic glomeruli. The in vitro study employed human mesangial cells exposed to 100 μg/mL AGE-BSA for 72 h in the presence of 1⁻20 μM chrysin. Glucose increased mesangial AGE production via induction of receptor for AGEs. Chrysin suppressed the induction of collagens, α-SMA, fibroblast-specific protein-1 and matrix metalloproteinases enhanced by AGE-bovine serum albumin. Furthermore, chrysin blunted transforming growth factor-β1 induction and Smad 2/3 activation in AGEs-exposed mesangial cells. These results demonstrate that chrysin attenuated accumulation of myofibroblast-like cells and matrix proteins in AGEs-laden diabetic glomeruli. Therefore, chrysin may be a potential renoprotective agent targeting glucose-mediated AGEs-associated glomerulosclerosis and fibrosis.

Topics: Animals; Blood Glucose; Cells, Cultured; Cytoprotection; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Models, Animal; Dose-Response Relationship, Drug; Extracellular Matrix; Fibrosis; Flavonoids; Glucose; Glycation End Products, Advanced; Humans; Mesangial Cells; Mice, Inbred C57BL; Receptor for Advanced Glycation End Products; Serum Albumin, Bovine; Signal Transduction; Smad Proteins, Receptor-Regulated; Transforming Growth Factor beta

Diabetes-associated visual cycle impairment has been implicated in diabetic retinopathy, and chronic hyperglycemia causes detrimental effects on visual function. Chrysin, a naturally occurring flavonoid found in various herbs, has anti-inflammatory, antioxidant, and neuroprotective properties. The goal of the current study was to identify the retinoprotective role of chrysin in maintaining robust retinoid visual cycle-related components. The in vitro study employed human retinal pigment epithelial (RPE) cells exposed to 33 mM of glucose or advanced glycation end products (AGEs) in the presence of 1⁻20 μM chrysin for three days. In the in vivo study, 10 mg/kg of chrysin was orally administrated to db/db mice. Treating chrysin reversed the glucose-induced production of vascular endothelial growth factor, insulin-like growth factor-1, and pigment epithelium-derived factor (PEDF) in RPE cells. The outer nuclear layer thickness of chrysin-exposed retina was enhanced. The oral gavage of chrysin augmented the levels of the visual cycle enzymes of RPE65, lecithin retinol acyltransferase (LRAT), retinol dehydrogenase 5 (RDH5), and rhodopsin diminished in db/db mouse retina. The diabetic tissue levels of the retinoid binding proteins and the receptor of the cellular retinol-binding protein, cellular retinaldehyde-binding protein-1, interphotoreceptor retinoid-binding protein and stimulated by retinoic acid 6 were restored to those of normal mouse retina. The presence of chrysin demoted AGE secretion and AGE receptor (RAGE) induction in glucose-exposed RPE cells and diabetic eyes. Chrysin inhibited the reduction of PEDF, RPE 65, LRAT, and RDH5 in 100 μg/mL of AGE-bovine serum albumin-exposed RPE cells. The treatment of RPE cells with chrysin reduced the activation of endoplasmic reticulum (ER) stress. Chrysin inhibited the impairment of the retinoid visual cycle through blocking ER stress via the AGE-RAGE activation in glucose-stimulated RPE cells and diabetic eyes. This is the first study demonstrating the protective effects of chrysin on the diabetes-associated malfunctioned visual cycle.

Topics: Animals; Cell Line; Diabetic Retinopathy; Disease Models, Animal; Endoplasmic Reticulum Stress; Epithelial Cells; Eye Proteins; Flavonoids; Glucose; Glycation End Products, Advanced; Humans; Male; Mice, Inbred C57BL; Protective Agents; Receptor for Advanced Glycation End Products; Retinal Pigment Epithelium; Serum Albumin, Bovine; Signal Transduction; Vision, Ocular

Interstitial fibrosis after acute myocardial infarction (MI) leads to cardiac structural remodeling and dysfunction. The peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist chrysin has been shown to protect injured myocardium through suppression of oxidative stress and inflammation. This study was designed to investigate the effect and mechanism of chrysin on myocardial fibrosis. A rat MI model was created by ligating the left coronary artery. The rats with MI were treated with chrysin (40 mg/kg/day) or 0.5% carboxymethylcellulose sodium by intragastric administration for 4 weeks after operation. The effect of chrysin on cardiac fibroblasts (CFs) were also assessed in vitro. Echocardiography showed that cardiac function was significantly improved after chrysin treatment. Chrysin reduced the levels of MDA and SOD and GSH-Px in myocardial tissue. Chrysin attenuated the interstitial and perivascular fibrosis and the expression of collagenlin the peri-infarcted zone and remarkably decreased the levels of matrix metalloproteinase-2 (MMP-2) and MMP-9. Chrysin up-regulated PPAR-γ and inhibited the nuclear factor-kappa B (NF-κB) pathway by suppressing inhibitor kappa B kinase β phosphorylation. Immunohistochemistry analysis and PCR detected downregulated expression of AP-1 after chrysin treatment. Chrysin also markedly reduced the increased α-SMA, typeland type III collagen expression of CFs mediated by AngII in vitro. In conclusion, chrysin has an antifibrosis cardioprotective effect on the infarct peripheral zone after MI. The underlined mechanism may be the up-regulation of PPAR-γ and inhibition of the NF-κB and AP1 pathway.

Topics: Animals; Disease Models, Animal; Fibroblasts; Fibrosis; Flavonoids; Heart; Myocardial Infarction; NF-kappa B; PPAR gamma; Rats; Transcription Factor AP-1; Up-Regulation

The constant increase in cardiovascular disease rate coupled with significant drawbacks of existing therapies emphasise the necessity to improve therapeutic strategies. Natural flavonoids exert innumerable pharmacological effects in humans. Here, we demonstrate the effects of chrysin, a natural flavonoid found largely in honey and passionflower on the modulation of platelet function, haemostasis and thrombosis. Chrysin displayed significant inhibitory effects on isolated platelets, however, its activity was substantially reduced under physiological conditions. In order to increase the efficacy of chrysin, a sulfur derivative (thio-chrysin), and ruthenium-complexes (Ru-chrysin and Ru-thio-chrysin) were synthesised and their effects on the modulation of platelet function were evaluated. Indeed, Ru-thio-chrysin displayed a 4-fold greater inhibition of platelet function and thrombus formation in vitro than chrysin under physiologically relevant conditions such as in platelet-rich plasma and whole blood. Notably, Ru-thio-chrysin exhibited similar efficacy to chrysin in the modulation of haemostasis in mice. Increased bioavailability and cell permeability of Ru-thio-chrysin compared to chrysin were found to be the basis for its enhanced activity. Together, these results demonstrate that Ru-thio-coupled natural compounds such as chrysin may serve as promising templates for the development of novel anti-thrombotic agents.

Topics: Animals; Biological Availability; Blood Platelets; Disease Models, Animal; Fibrinolytic Agents; Flavonoids; Hemostasis; Humans; Mice; Platelet Activation; Ruthenium; Thrombosis

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Aspartate Aminotransferases; Biomarkers; Colony Count, Microbial; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Flavonoids; Gene Expression; Kaempferols; Leukocyte Count; Liver; Male; Mice; Mice, Inbred ICR; Nitric Oxide; Peroxidase; Sepsis; Survival Analysis; Tumor Necrosis Factor-alpha

Asthma is a chronic airway inflammatory disorder and progresses mainly due to airway remodeling. Chrysin, a natural flavonoid, has been reported to possess multiple biologic activities, including anti-inflammation, anti-oxidation and anti-proliferation. The present study aimed to investigate whether chrysin could relieve allergic airway inflammation and remodeling in a murine model of chronic asthma and the mechanism involved. The female BALB/c mice sensitized and challenged with ovalbumin (OVA) successfully developed airway hyperresponsiveness (AHR), inflammation and remodeling. The experimental data showed that chrysin could alleviate OVA-induced AHR. Chrysin could also reduce OVA-induced increases in the number of inflammatory cells, especially eosinophils, interleukin (IL) -4, and IL-13 in bronchoalveolar lavage fluid (BALF) and total IgE in serum. The decreased interferon-γ (IFN-γ) level in BALF was also upregulated by chrysin. In addition, inflammatory cell infiltration, goblet cell hyperplasia and the expression of α-smooth muscle actin (α-SMA) around bronchioles were suppressed by chrysin. Furthermore, the phosphorylation levels of Akt and extracellular signal-regulated kinase (ERK) could be decreased by chrysin, which are associated with airway smooth muscle cell (ASMC) proliferation. These results indicate the promising therapeutic effect of chrysin on chronic asthma, especially the progression of airway remodeling.

Topics: Acetylcholine; Airway Remodeling; Allergens; Animals; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Female; Flavonoids; Immunoglobulin E; Lung; Mice; Mice, Inbred BALB C; Muscle, Smooth; Ovalbumin; Proto-Oncogene Proteins c-akt

To study the therapeutic effect of chrysin, a flavonoid with strong antioxidant and anti-inflammatory activities, on adenine-induced chronic kidney diseases (CKD) in rats.. Chrysin, in three graded oral doses (10, 50 and 250 mg/kg), was given for 10 consecutive days to rats after the induction of CKD by feeding them adenine (0.25%(w/w) for 35 days). Several plasma and urine biomarkers and tissues morphology were used the investigate chrysin effect on kidney structure and function.. Adenine lowered creatinine clearance and elevated the concentrations of urea, creatinine, plasma neutrophil gelatinase-associated lipocalin and urinary N-Acetyl-beta-D-glucosaminidase activity, and increased the concentrations of the uremic toxin indoxyl sulfate, in addition to some inflammatory cytokines. Renal histopathological markers of inflammation and fibrosis were significantly increased. Renal catalase and superoxide dismutase activities, total antioxidant capacity and reduced glutathione were all adversely affected. Most of these adenine - induced actions were moderately mitigated by chrysin, especially at the highest dose. Compared to control, chrysin did not cause any overt adverse effects on the treated rats.. Different doses of chrysin produce variable therapeutic salutary effects in rats with CKD, and that, pending further studies, its usability as a possible therapeutic agent in human CKD should be considered.

Topics: Acute-Phase Proteins; Adenine; Administration, Oral; Animals; Antioxidants; Biomarkers; Catalase; Creatinine; Cytokines; Disease Models, Animal; Flavonoids; Glutathione; Kidney; Lipocalin-2; Lipocalins; Proto-Oncogene Proteins; Rats; Renal Insufficiency, Chronic; Superoxide Dismutase; Urea

Chemoprevention is considered as one of the most promising and realistic approaches in the prevention of lung cancer. Chrysin, a naturally occurring dietary flavone widely found in Passiflora family of plants and honey, has been studied extensively for its chemopreventive properties. The objective of present study is to divulge the chemopreventive role of chrysin against benzo(a)pyrene [B(a)P] induced lung carcinogenesis in Swiss albino mice.. B(a)P was administered orally (50mg/kg body weight) twice a week for four weeks to induce lung cancer in mice. The body weight, lung weight, tumor incidence, lipid peroxidation, carcinoembryonic antigen, enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase) and non-enzymatic antioxidants (reduced glutathione, vitamin E and vitamin C) were estimated. Further, histopathological analysis of lung tissue and western blotting analysis of PCNA, COX-2 and NF-κB were also carried out.. Administration of B(a)P resulted in increased lipid peroxides and carcinoembryonic antigen with concomitant decrease in the levels of both enzymatic antioxidants and non-enzymatic antioxidants. Chrysin treatment (250mg/kg body weight) significantly attenuated all these changes thereby showing potent anti lung cancer effect. Further, the anticancer effect of chrysin was confirmed by histopathology of lungs, and immunoblotting analysis of PCNA, COX-2 and NF-κB, where chrysin supplementation downregulated the expression of these proteins and maintained cellular homeostasis.. Overall, these findings confirm the chemopreventive potential of chrysin against B(a)P induced lung cancer in Swiss albino mice.

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; Benzo(a)pyrene; Carcinogenesis; Catalase; Chemoprevention; Diet; Disease Models, Animal; Flavones; Flavonoids; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Lipid Peroxidation; Lung; Lung Neoplasms; Male; Mice; NF-kappa B; Superoxide Dismutase; Vitamin E

The aim of this study was to evaluate the effect of chrysin on laser-induced experimental choroidal neovascularization (CNV) in a rat model.. Male brown Norway rats were anesthetized, and a diode laser was used to break Bruch's membrane. One week later, each rat was intravitreally injected with 5 µl of 15 mg/ml chrysin, and CNV development was determined by fluorescein angiography at 2 weeks. The effect of chrysin on experimental CNV was assessed by fluorescein angiography and histology.. Two weeks after laser treatment, the intensity of fluorescein leakage from the photocoagulated lesions decreased significantly compared with the control group (p = 0.044). When the lesions were categorized into low- and high-leakage groups, there was a significant correlation between chrysin treatment and degree of leakage (p = 0.028). Compared with the chrysin-treated group, the relative risk of developing high-leakage lesions in the control group was 3.18. The mean CNV thickness was significantly thinner in chrysin-treated eyes than in control eyes (34.13 ±.0.88 vs. 37.76 ± 0.90 μm, p = 0.005).. Chrysin has an inhibitory effect on CNV in an experimental rat model, indicating that chrysin should be further evaluated for its potential as a therapy for CNV in age-related macular degeneration and in other vision-threatening conditions associated with CNV.

Topics: Animals; Choroidal Neovascularization; Disease Models, Animal; Flavonoids; Fluorescein Angiography; Fundus Oculi; Intravitreal Injections; Male; Rats; Rats, Inbred BN; Treatment Outcome; Vascular Endothelial Growth Factor A

Chrysin, a flavonoid compound existing in several plants, is applied as a dietary supplement because of its beneficial effects on general human health and alleviation of neurological disorders. However, mechanisms underlying neuroprotection of chrysin has not been fully elucidated, and the effects of chrysin on the Parkinson's disease (PD) model in vivo have not been investigated. It is here shown that chrysin protects primary granular neurons against 1-methyl-4-phenylpyridinium ion insult via antiapoptosis by reversing the dysregulated expression of Bcl-2, Bax, and caspase 3. The mechanisms also involved activating transcriptional factor myocyte enhancer factor 2D (MEF2D) via regulation of AKT-GSK3β signaling. In this in vivo model of PD, chrysin rescued the dopaminergic neurons loss and alleviated the decrease in dopamine level induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice. Moreover, chrysin markedly inhibited monoamine oxidase-B activity in vitro and in vivo. In conclusion, chrysin exerts beneficial effects to PD, possibly through multitarget mechanisms including antineuronal apoptosis, activation of the AKT-GSK3β/MEF2D pathway, and inhibition of the MAO-B activity.

Topics: Animals; Apoptosis; Cells, Cultured; Disease Models, Animal; Flavonoids; Humans; Male; MEF2 Transcription Factors; Mice; Mice, Inbred C57BL; Monoamine Oxidase; Neurons; Parkinson Disease; Rats; Rats, Sprague-Dawley

3-Nitropropionic acid (3-NP) is an irreversible inhibitor of mitochondrial complex-II that causes transcriptional dysregulation, bioenergetics failure, protein aggregation and oxidative damage similar to Huntington's disease (HD) pathogenesis. Chrysin, a bioactive flavonoid reported to have anti-inflammation, antioxidant, vasorelaxant and neuroprotective property. The present study was framed to determine the neuroprotective efficiency of chrysin upon 3-NP induced oxidative stress, mitochondrial dysfunctions and neurodegeneration. 3-NP (10mg/kg b.w. i.p.) administration for 14days exhibited significant (P<0.01) behavioral alterations, mitochondrial dysfunction and oxidative damages to biomolecules, finally causes cell death. Chrysin at 50mg/kg b.w. orally for 14days improved all the behavioral performances and regulated the complex activities in mitochondria. Further, chrysin diminished the oxidative stress markers (lipid peroxidation, nitrite and protein carbonyls) by significantly (P<0.01) improving the antioxidant status (superoxide dismutase, catalase and reduced glutathione) in striatal mitochondria. Indeed, chrysin prevents apoptosis by upregulating the Bcl-2 mRNA expression and downregulating the pro-apoptotic (Bax, Bad) mRNAs in 3-NP induced condition. Furthermore, the survival of striatal neurons against 3-NP toxicity was enhanced upon chrysin treatment which was evidenced by observing histopathological studies. Hence, the present study collectively suggests that the chrysin can serve as a potential therapeutic agent on 3-NP induced mitochondrial deficits and subsequent apoptosis.

Topics: Animals; Apoptosis; Basal Ganglia; bcl-2-Associated X Protein; bcl-Associated Death Protein; Behavior, Animal; Biomarkers; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Flavonoids; Huntington Disease; Male; Maze Learning; Mitochondrial Diseases; Mitochondrial Swelling; Motor Activity; Nerve Degeneration; Neuroprotective Agents; Nitro Compounds; Oxidative Stress; Postural Balance; Propionates; Proto-Oncogene Proteins c-bcl-2; Rats, Wistar; Signal Transduction; Time Factors; Up-Regulation

Our working hypothesis is that brain neurotrophins and brain Na(+),K(+)-ATPase may be strongly associated with the occurrence of depression in animals subjected to chronic unpredictable mild stress (CUMS). Still, we believe that chrysin, a natural and bioactive flavonoid found in honey and some plants, can provide satisfactory effects on antidepressant therapy. Thus, we aimed to evaluate the effect of CUMS on brain-derived neurotropic factor (BDNF) and nerve growth factor (NGF) levels as well as the Na(+),K(+)-ATPase activity in the hippocampus and prefrontal cortex of female mice. We also aimed to examine the effect of a 28-day oral treatment with chrysin (5 or 20mg/kg) in female mice subjected to CUMS, comparing to the effect of fluoxetine. Results showed that CUMS applied for 28days induced a decrease in BDNF and NGF levels as well as in the Na(+),K(+)-ATPase activity. CUMS also promoted a depressive status in the swimming forced test (FST), in the sucrose preference test, and in corticosterone levels. Chrysin (20mg/kg) and fluoxetine also occasioned the up-regulation of BDNF and NGF levels in non-stressed mice and in mice subjected to CUMS. CUMS decreased non-protein thiol (NPSH) levels and increased reactive oxygen species (ROS) levels. In response to these changes, the glutathione reductase (GR), glutathione peroxidase (GPx) and catalase (CAT) activities were increased in mice exposed to CUMS. Chrysin and fluoxetine treatments protected against all these alterations, suggesting the involvement of the antioxidant function in the antidepressant effect of chrysin and fluoxetine. In conclusion, CUMS decreased BDNF and NGF levels as well as the Na(+),K(+)-ATPase activity in mice. Chrysin presented antidepressant effect in mice on behavioral, neurotrophic and biochemistry parameters equivalent to fluoxetine. Furthermore, we suggest that the up-regulation of BDNF and NGF levels is a mechanism possibly involved in the antidepressant effect of chrysin in mice.

Topics: Animals; Antidepressive Agents; Antioxidants; Brain-Derived Neurotrophic Factor; Catalase; Chronic Disease; Corticosterone; Depressive Disorder; Disease Models, Animal; Female; Flavonoids; Fluoxetine; Glutathione Peroxidase; Glutathione Reductase; Hippocampus; Mice, Inbred C57BL; Nerve Growth Factor; Prefrontal Cortex; Sodium-Potassium-Exchanging ATPase; Stress, Psychological; Uncertainty; Up-Regulation

Chrysin (5, 7- dihydroxyflavone) is a flavonoid with several pharmacological properties that include antioxidant, anti-inflammatory and antiapoptotic activities. in this work, we investigated some effects of three graded oral doses of chrysin (10, 50 and 250 mg/kg) on kidney structure and function in rats with experimental chronic renal disease (CKD) induced by adenine (0.25% w/w in feed for 35 days), which is known to involve inflammation and oxidative stress. Using several indices in plasma, urine and kidney homogenates, adenine was found to impair kidney function as it lowered creatinine clearance and increased plasma concentrations of creatinine, urea, neutrophil gelatinase-associated lipocalin and N-Acetyl-beta-D-glucosaminidase activity. Furthermore, it raised plasma concentrations of the uremic toxin indoxyl sulfate, some inflammatory cytokines and urinary albumin concentration. Renal morphology was severely damaged and histopathological markers of inflammation and fibrosis were especially increased. In renal homogenates, antioxidant indices, including superoxide dismutase and catalase activities, total antioxidant capacity and reduced glutathione were all adversely affected. Most of these adenine - induced actions were moderately and dose -dependently mitigated by chrysin, especially at the highest dose. Chrysin did not cause any overt adverse effect on the treated rats. The results suggest that different doses of chrysin produce variable salutary effects against adenine-induced CKD in rats, and that, pending further pharmacological and toxicological studies, its usability as a possible ameliorative agent in human CKD should be considered.

Topics: Acetylglucosaminidase; Adenine; Animals; Antioxidants; Creatinine; Disease Models, Animal; Fibrosis; Flavonoids; Inflammation; Kidney; Kidney Function Tests; Lipocalins; Male; Neutrophils; Oxidative Stress; Rats; Rats, Wistar; Renal Insufficiency, Chronic; Urea

To explore the therapeutic effects of chrysin for steroid-resistant asthma in a murine model.. Lipopolysaccharide (LPS) was used to induce steroid-resistant asthma in a murine model sensitized and challenged with ovalbumin (OVA). Forty-eight female BALB/c mice were randomly divided into 6 groups of control (A), OVA (B), LPS + OVA (C), LPS + OVA + dexamethasone (D), LPS + OVA + chrysin (E) and LPS + OVA + dexamethasone + chrysin (F) (n = 8 each). At Day 1 and 14, group A received an intraperitoneal injection of phosphate buffered saline (PBS); groups B, C, D, E and F had an intraperitoneal injection of a mixture of OVA (20 µg) and aluminum hydroxide for sensitization. At Day 27, groups A and B were intranasally instilled with PBS while groups C, D, E and F had an intranasal instillation of LPS (10 µg). At Days 28, 29 and 30, groups B, C, D, E and F were challenged via airway with 1% OVA in PBS for 30 min and group A with PBS. Group D was intraperitoneally injected with dexamethasone (3 mg/kg) 30 min pre-challenge and PBS one day pre-challenge; group E received an intraperitoneal injection of chrysin (50 mg/kg) at one day and 1h pre-challenge; group F received dexamethasone (3 mg/kg) 30 min pre-challenge and chrysin (50 mg/kg) at one day and 1 h pre-challenge; groups A, B and C had PBS as above. Hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining of lung tissues were performed to observe the pathologic changes. The total cells in bronchoalveolar lavage fluid (BALF) were counted under microscope. And enzyme-linked immunosorbent assay (ELISA) was applied for detecting interleukin-4 (IL-4) and interleukin-13 (IL-13) in BALF and IgE in sera.. The inflammatory infiltration in lung tissue of group F was obviously suppressed compared with that of group C. The numbers of PAS-positive cells per bronchus divided by the total number of epithelial cells in group D, E, F were markedly lower than that in group C ((54.5 ± 6.9)%, (53.3 ± 8.2)%, (23.8 ± 7.0)% vs (71.3 ± 12.2)%, all P < 0.01). The total cells in BALF of group E and F significantly decreased versus that of group C ((1.22 ± 0.23) × 10⁴/ml, (0.98 ± 0.25) × 10⁴/ml vs (2.56 ± 0.18) × 10⁴/ml, both P < 0.01). The levels of IL-4 in group D and F were significantly less than that of group C ((118 ± 7), (124 ± 5) vs (138 ± 6) pg/ml, both P < 0.01). The levels of IL-13 in BALF of group E and F significantly decreased compared with that of group C ((787 ± 57), (484 ± 32) vs (1 121 ± 132) pg/ml, both P < 0.01). The levels of IgE in sera of group D, E, F were significantly lower those of group C ((10 310 ± 494), (10 771 ± 650), (7 529 ± 485) vs (12 618 ± 595) ng/ml, all P < 0.01).. Chrysin could improve the therapeutic efficacies of glucocorticoid for steroid-resistant asthma.

Topics: Animals; Asthma; Bronchi; Bronchoalveolar Lavage Fluid; Dexamethasone; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Flavonoids; Glucocorticoids; Injections, Intraperitoneal; Lipopolysaccharides; Lung; Mice; Mice, Inbred BALB C; Ovalbumin

The aim of the present study is to investigate the protective effect of chrysin (5,7-dihydroxyflavone) on right ventricular remodeling in a rat model of monocrotaline-induced pulmonary arterial hypertension (PAH). PAH rats were induced by a single injection of monocrotaline (60 mg x kg(-1), sc) and were administered with chrysin (50 or 100 mg x kg(-1) x d(-1)) for 4 weeks. At the end of experiment, the right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (mPAP) were monitored via the right jugular vein catheterization into the right ventricle. Right ventricle (RV) to left ventricle (LV) + septum (S) and RV to tibial length were calculated. Right ventricular morphological change was observed by HE staining. Masson's trichrome stain was used to demonstrate collagen deposition. The total antioxidative capacity (T-AOC) and malondialdehyde (MDA) levels in right ventricle were determined according to the manufacturer's instructions. The expressions of collagen I, collagen III, NADPH oxidase 4 (NOX4) and nuclear factor-kappa B (NF-κB) were analyzed by immunohistochemisty, qPCR and (or) Western blot. The results showed that chrysin treatment for 4 weeks attenuated RVSP, mPAP and right ventricular remodeling index (RV/LV+S and RV/Tibial length) of PAH rats induced by monocrotaline. Furthermore, monocrotaline-induced right ventricular collagen accumulation and collagen I and collagen III expression were both significantly suppressed by chrysin. The expressions of NOX4, NF-κB and MDA contents were obviously decreased, while the T-AOC was significantly increased in right ventricule from PAH rats with chrysin treatment. These results suggest that chrysin ameliorates right ventricular remodeling of PAH induced by monocrotaline in rats through its down-regulating of NOX4 expression and antioxidant activity, and inhibiting NF-κB expression and collagen accumulation.

Topics: Animals; Blotting, Western; Collagen; Disease Models, Animal; Flavonoids; Heart Ventricles; Hypertension, Pulmonary; Monocrotaline; NADPH Oxidase 4; NADPH Oxidases; NF-kappa B; Rats; Ventricular Remodeling

Reactive oxygen species play a role in a number of degenerative conditions including osteoporosis. Flavonoids as phyto-oestrogens exert physiological effects against oxidative stress diseases. We developed a retinoic acid-induced bone loss model of rats to assess whether flavonoids and alendronate as positive control have role against oxidative stress and mineral contents in osteoporosis in vivo.. Three-month-old female rats of the Y59 strain were given quercetin, chrysin, naringenin (100 mg kg(-1)) or alendronate (40 mg kg(-1), a positive control) immediately before retinoic acid treatment (80 mg kg(-1)) once daily for 14 days by a single intragastric (i.g.) application. In the second part of the study, we assessed the effect of those flavonoids on the skeletal system of healthy rats using single i.g. application on the respective flavonoids during 14 days. Twenty-four hours after the treatment, we analysed bone mineral density and the total content of bone calcium and phosphorus in the femur, the geometric and physical characteristics of thigh bones and lipid peroxidation and glutathione levels of liver and kidney cells.. All flavonoids improved the decrease in bone weight coefficient, the length and the diameter of the bone, the content of bone ash and calcium and phosphorus content induced by retinoic acid. Chrysin and quercetin showed promise as preventive agents. Flavonoids were superior to alendronate according to some criteria.. These results suggest that the dietary flavonoids could reduce retinoic acid-induced oxidative stress and bone loss and that flavonoids may be useful therapeutics for prevention of skeletal diseases.

Topics: Animals; Bone Density; Calcium; Disease Models, Animal; Female; Femur; Flavanones; Flavonoids; Lipid Peroxidation; Minerals; Osteoporosis; Oxidative Stress; Phosphorus; Quercetin; Rats; Tretinoin

Chrysin (CH) is an important natural plant flavonoid and possesses diverse pharmacological activities. Our present investigations aimed to assess the neuroprotection of CH against diabetes-associated cognitive decline (DACD) in a rat model of diabetes and exploring its potential mechanism. Diabetic model was induced by intraperitoneal injection of streptozotocin. Then, they were treated with vehicle or CH by doses of 30 and 100 mg/kg for 26 days. Learning and memory function was evaluated by Morris water maze test. The oxidative indicators [malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH)], NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 were measured in cerebral cortex and hippocampus using corresponding commercial kits. The diabetic rats showed marked reductions in body weight, percentage of time spent in target quadrant and number of times of crossing platform, coupled with increases in plasma glucose levels, escape latency, mean path length and oxidative stress (increased MDA level and decreased CAT and SOD as well as reduced GSH), NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 in cerebral cortex and hippocampus. Moreover, CH supplement dramatically reversed the corresponding behavioral, biochemical and molecular alterations in diabetes. The alterations of swimming speed among different groups were not observed after CH adminstration. In conclusion, our current work discloses that CH remarkably alleviates DACD and suggests that oxidative stress, inflammation and apoptotic cascades are linked with diabetes-associated cognitive deficits. These findings point toward the therapeutic potential of CH in DACD.

Topics: Animals; Blood Glucose; Body Weight; Cerebral Cortex; Cognition Disorders; Diabetes Complications; Disease Models, Animal; Encephalitis; Flavonoids; Male; Maze Learning; Oxidative Stress; Rats; Rats, Wistar; Streptozocin

To evaluate the putative protective role of chrysin, an isoflavone, on D-galactose-induced aging in an experimental rat model.. Rats were divided into five groups of five each. Group I received 0.9% saline only. Groups II, III and IV received d-galactose (50 mg/kg bodyweight) intraperitoneally, additionally group III and group IV received chrysin (20 mg/kg bodyweight) and α-tocopherol acetate (200 mg/kg bodyweight), respectively. Group V received chrysin alone. The experiment period was for a period of 8 weeks. After the rats were killed, the tissue samples were analyzed for mean activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, glucose-6-phosphate dehydrogenase, reduced glutathione, vitamin C, vitamin E, malondialdehyde and protein carbonyl. Histopathological studies were also carried out for morphological conformation.. Tissue samples from D-galactose-exposed untreated rats showed significantly (P < 0.05) lower levels of enzymatic and non-enzymatic anti-oxidants, and significantly (P < 0.05) higher levels of malondialdehyde and protein carbonyl when compared with group I and group III rats. Oral administration of chrysin for a period of 8 weeks, concomitant with the exposure to D-galactose, appeared to protect against oxidative damage and maintained all parameters at near normal levels. Histopathological studies confirmed the oxidative damage caused by D-galactose alone in tissues and also showed the tissue protective role of chrysin in rats receiving D-galactose and chrysin.. These results suggest that chrysin protects against oxidative stress-induced tissue damage in D-galactose-induced aging in an experimental rat model.

Topics: Aging; Analysis of Variance; Animals; Ascorbic Acid; Catalase; Disease Models, Animal; Flavonoids; Galactose; Glucosephosphate Dehydrogenase; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Glutathione Transferase; Male; Malondialdehyde; Oxidative Stress; Protein Carbonylation; Rats; Rats, Wistar; Superoxide Dismutase

Chrysin, a flavonoid obtained from various natural sources, has been reported to possess anti-inflammatory, antitumor, antioxidant and anti-allergic activities. However, its anti-inflammatory and immunoregulatory activities in asthma animal models are poorly understood. In the present study, we examined the effects of chrysin on airway inflammation and the possible mechanisms through which it acts in a murine model of allergic asthma. BALB/c mice sensitized and challenged to ovalbumin (OVA) were administered intragastrically with chrysin at a dose of 50 mg/kg daily. Chrysin significantly suppressed OVA-induced airway hyperresponsiveness (AHR) to acetylcholine chloride (Ach). Chrysin administration significantly inhibited the total inflammatory cell and eosinophil counts in bronchoalveolar lavage fluid (BALF) and total immunoglobulin E (IgE) levels in serum. Histological examination of lung tissue demonstrated that chrysin significantly attenuated allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells in the airway. In addition, chrysin triggered a switch of the immune response to allergens towards a T-helper type 1 (Th1) profile by modulating the transcription factors T-bet and GATA-3 in allergic mice. These data suggest that chrysin exhibits anti-inflammatory and immunoregulatory properties and provides new insights into the immunopharmacological role of chrysin in terms of its effects in a murine model of asthma.

Topics: Animals; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Female; Flavonoids; GATA3 Transcription Factor; Immunoglobulin E; Inflammation; Lung; Mice; Mice, Inbred BALB C; Ovalbumin; T-Box Domain Proteins; Th1 Cells; Th2 Cells

Chrysin, a natural flavonoid has been reported to possess potent anti-inflammatory, anti-cancer and antioxidation properties. In the present study, we aimed to evaluate the putative protective effect of chrysin, an isoflavone, on carbon tetrachloride (CCl(4))-induced toxicity in male Wistar rats. Intraperitoneal administration of CCl(4) (2 ml/kg) to rats for 4 days resulted in significantly elevated (p < 0.05) serum levels of glutamic oxaloacetic transaminase (SGOT), glutamic pyruvate transaminase (SGPT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), when compared to normal rats. In addition, the tissues (liver, kidney and brain) and haemolysate samples showed considerable increase in levels (p < 0.05) of malondialdehyde (MDA) and lowered levels (p < 0.05) of reduced glutathione (GSH), vitamin C and E when compared to values in normal rats. Quantitative analysis of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (Gpx) exhibited lower activities of these antioxidant enzymes in the tissues and haemolysate of CCl(4)-administered rats. The protective action of chrysin on CCl(4)-induced rat was demonstrated with SGPT, SGOT, ALP and LDH resuming to near normal levels, while the mean levels of GSH and of vitamin C and E were elevated, the mean activities of CAT, SOD and Gpx were enhanced and the mean level of MDA was lowered in the tissue and haemolysate samples when compared to the CCl(4)-exposed untreated rats. The expression of the iNOS gene appeared to be up-regulated in the liver and kidney samples of CCl(4)-exposed untreated rats, whereas in CCl(4)-exposed chrysin-treated rats, the mRNA transcript levels of iNOS approximated normal levels. These results strongly suggest that chrysin is able to prevent the oxidative damage induced by CCl(4) in the liver, brain, kidney and haemolysate of male Wistar rats.

Topics: Animals; Antioxidants; Ascorbic Acid; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Flavonoids; Kidney; Liver; Liver Function Tests; Male; Malondialdehyde; Nitric Oxide Synthase Type II; Oxidoreductases; Rats; Rats, Wistar; RNA, Messenger; Up-Regulation; Vitamin E

Chemical investigation of the stem bark of Oroxylum indicum resulted in the isolation and characterization of two new flavonoid glycosides (1, 2), along with seven known compounds (3-9). Their structures were established on the basis of extensive spectroscopic (IR, MS, 2D NMR) data analysis and by the comparison with spectroscopic data reported in the literature. In addition, all the compounds were tested for their ulcer protective effects against various gastric ulceritis inducing models in rats.

Topics: Animals; Anti-Ulcer Agents; Bignoniaceae; Disease Models, Animal; Flavanones; Flavones; Flavonoids; Magnetic Resonance Spectroscopy; Plant Bark; Plant Stems; Rats

We evaluated the antifilarial activity of 6 flavonoids against the human lymphatic filarial parasite Brugia malayi using an in vitro motility assay with adult worms and microfilariae, a biochemical test for viability (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT)-reduction assay), and two animal models, Meriones unguiculatus (implanted adult worms) and Mastomys coucha (natural infections). In vitro, naringenin and hesperetin killed the adult worms and inhibited (>60%) MTT-reduction at 7.8 and 31.2 μg/ml concentration, respectively. Microfilariae (mf) were killed at 250-500 μg/ml. The half maximal inhibitory concentration (IC(50)) of naringenin for motility of adult females was 2.5 μg/ml. Flavone immobilized female adult worms at 31.2 μg/ml (MTT>80%) and microfilariae at 62.5 μg/ml. Rutin killed microfilariae at 125 μg/ml and inhibited MTT-reduction in female worms for >65% at 500 μg/ml. Naringin had adulticidal effects at 125 μg/ml while chrysin killed microfilariae at 250 μg/ml. In vivo, 50 mg/kg of naringenin elimiated 73% of transplanted adult worms in the Meriones model, but had no effect on the microfilariae in their peritoneal cavity. In Mastomys, the same drug was less effective, killing only 31% of the naturally acquired adult worms, but 51%, when the dose was doubled. Still, effects on the microfilariae in the blood were hardly detectable, even at the highest dose. In summary, all 6 flavonoids showed antifilarial activity in vitro, which can be classed, in a decreasing order: naringenin>flavone=hesperetin>rutin>naringin>chrysin. In jirds, naringenin and flavone killed or sterilized adult worms at 50mg/kg dose, but in Mastomys, where the parasite produces a patent infection, only naringenin was filaricidal. Thus naringenin and flavone may provide a lead for design and development of new antifilarial agent(s). This is the first report on antifilarial efficacy of flavonoids.

Topics: Animals; Brugia malayi; Coloring Agents; Disease Models, Animal; Elephantiasis, Filarial; Female; Filaricides; Flavanones; Flavonoids; Gerbillinae; Hesperidin; Humans; Male; Murinae; Rutin; Survival Analysis; Tetrazolium Salts; Thiazoles

Chrysin (5,7-dihydroxyflavone) is a natural flavone commonly found in many plants. It has previously been shown to be an anti-tumor agent. In this study, we investigated whether chrysin could alleviate the symptoms of dextran sodium sulfate (DSS)-induced colitis in mice and whether chrysin has an inhibitory effect on nuclear factor (NF)-kappaB activation in vitro. A significant blunting of weight loss and clinical signs was observed in DSS-exposed, chrysin-treated mice when compared to vehicle-treated mice. This was associated with a remarkable amelioration of the disruption of the colonic architecture, a significant reduction in colonic myeloperoxidase (MPO) activity, and a decrease in the production of inflammatory mediators such as nitric oxide (NO), prostaglandin (PG) E(2), and pro-inflammatory cytokines. In addition, chrysin inhibited tumor necrosis factor (TNF)-alpha-induced activation of NF-kappaB in IEC-6 cells. These findings suggest that chrysin exerts potentially clinically useful anti-inflammatory effects mediated through the suppression of NF-kappaB activation.

Topics: Animals; Colon; Dextran Sulfate; Disease Models, Animal; Flavonoids; I-kappa B Proteins; Inflammation Mediators; Inflammatory Bowel Diseases; Intestinal Mucosa; Mice; Mice, Inbred BALB C; Protein Transport; Weight Loss

Chrysin, a passion flower extract, may be beneficial because of its potential to attenuate surgical suppression of natural killer (NK) cell activity. We divided 37 male Sprague-Dawley rats into 3 treatment groups: (1) rats undergoing abdominal surgery and administered isoflurane and a 5% solution of dimethyl sulfoxide in saline (vehicle), (2) rats undergoing abdominal surgery and administered isoflurane and chrysin solubilized in 5% dimethyl sulfoxide, and (3) rats not undergoing surgery but administered isoflurane and chrysin. Natural killer cell activity was measured before and 24 hours after the experiment. Analysis of covariance, with preoperative NK cell activity as the covariate, was used to compare differences in NK cell activity among groups. The Scheffe procedure was used to make post hoc comparisons. Analysis revealed a significant difference (P = .006) such that group 2 had significantly less NK cell suppression compared with groups 1 and 3. These findings suggest that chrysin may attenuate surgical suppression of NK cell activity, thereby minimizing metastatic spread of cancer.

Topics: Administration, Inhalation; Analysis of Variance; Anesthetics, Inhalation; Animals; Dimethyl Sulfoxide; Disease Models, Animal; Drug Evaluation, Preclinical; Flavonoids; GABA Agonists; Immune Tolerance; Isoflurane; Killer Cells, Natural; Laparotomy; Lymphocyte Count; Male; Passiflora; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Solvents; Time Factors

The definitive anxiolytic effects of Passiflora incarnata are unknown. We studied the potential anxiolytic effects of chrysin, a Passiflora extract, and the purported modulation of the benzodiazepine receptor on the GABA(A) receptor in laboratory rats. We hypothesized that chrysin decreases anxiety via interaction with the GABA(A) receptor in laboratory rats as measured by elevated plus-maze (EPM), corticosterone, and catecholamine assays. We randomized 44 male Sprague-Dawley rats in a double-blind, placebo-controlled, between-subjects experimental design. Each animal received an intraperitoneal injection of (1) vehicle (DMSO 4%), (2) chrysin, 2 mg/kg, (3) midazolam, 1.5 mg/kg, or (4) flumazenil, 3 mg/kg and chrysin, 2 mg/kg. The EPM was used to evaluate the behavioral component of anxiolysis, and catecholamine and corticosterone assays were examined to measure the neurohormonal effects of anxiety. No statistical difference was found among groups in catecholamine and corticosterone levels. Midazolam significantly decreased anxiety compared with control and flumazenil plus chrysin groups (P <.05); there was no significant difference compared with the chrysin group. These data suggest that chrysin may have anxiolytic properties similar to midazolam but to a lesser magnitude at the 2 mg/kg dose used in this study.

Topics: Analysis of Variance; Animals; Anti-Anxiety Agents; Anxiety; Behavior, Animal; Catecholamines; Corticosterone; Dimethyl Sulfoxide; Disease Models, Animal; Double-Blind Method; Drug Evaluation, Preclinical; Flavonoids; Flumazenil; Male; Maze Learning; Midazolam; Passiflora; Phytotherapy; Plant Extracts; Random Allocation; Rats; Rats, Sprague-Dawley; Receptors, GABA-A

The xanthine oxidase (XOD) inhibitory activity of propolis from China and Brazil was measured. The propolis from both place were seen to have XOD inhibitory activity. However, a stronger tendency was shown in the propolis from China. The compounds in each the propolis were measured quantitatively. A great deal of chrysin, galangin, and caffeic acid phenetyl ester were found in the propolis from China, an abundance of p-coumaric acid and artepillin C in the propolis from Brazil. Therefore it was revealed that the propolis compounds are very different depending on their place of origin. The XOD inhibitory activity of these five compounds was measured. Caffeic acid phenetyl ester had the strongest activity, with chrysin and galangin next; p-coumaric acid and artepillin C showed weak XOD inhibitory activity. We evaluated the hypouricemic effect of propolis from China on hyperuricemia induced by the uricase inhibitor, oxonic acid (500 mg/kg p.o., 1 h before the test drugs), and measured plasma uric acid values in rats. Oral propolis had a hypouricemic effect 2 h after its administration to oxonate-pretreated rats. These results suggested that a continuous intake of propolis may be effective for the prevention and the treatment of gout and hyperuricemia.

Topics: Animals; Anti-Infective Agents; Brazil; Caffeic Acids; China; Coumaric Acids; Disease Models, Animal; Flavonoids; Gout; Hyperuricemia; Male; Oxonic Acid; Phenylethyl Alcohol; Phenylpropionates; Propionates; Propolis; Rats; Rats, Sprague-Dawley; Uric Acid; Xanthine Oxidase